Page 15 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 2 of 16 Guideline

8,9
role of corticosteroids in CM. Finally, international and 12. Antifungal susceptibility testing is now recommended if
local advocacy efforts have resulted in increasing, yet still a patient has a single relapse episode of CM and other
limited, access to flucytosine and a reduced cost of liposomal causes have been excluded.
amphotericin B for the treatment of CM. 10
Recommendation 1: Cryptococcal
Summary of major changes to the guideline antigen screening and pre-emptive
1. We now recommend CrAg screening for all adults or treatment
adolescents with a CD4 T-lymphocyte (CD4) count
+ Background
< 200 cells/µL who are initiating ART for the first time,
switching after ART failure or re-entering into care after Early diagnosis of HIV infection and early initiation of ART
prior disengagement. before immunosuppression is the most important strategy
2. Reflex laboratory CrAg screening is recommended as the to reduce the incidence of CM and CM-associated mortality.
preferred approach in South Africa, although alternative In South Africa, patients should initiate ART according to
approaches may be more suitable for other countries in the current national guideline. 1,11,12 Screening for subclinical
Southern Africa. cryptococcal disease has a proven mortality benefit among
3. To diagnose CM, lumbar puncture (LP) is recommended HIV-seropositive patients with low CD4 counts. In the
for all patients with a new positive CrAg screening test Reduction of Early Mortality among HIV-infected Subjects
result. sTarting AntiRetroviral Therapy (REMSTART) trial, HIV-
4. The recommended induction regimen for CM is 1 week of seropositive outpatients with a CD4 count < 200 cells/µL,
amphotericin B deoxycholate (1 mg/kg/day) and who were randomised to receive CrAg screening and
flucytosine (100 mg/kg/day in four divided doses), community-based ART adherence support, had a 28%
followed by 1 week of fluconazole (1200 mg daily for reduced all-cause mortality rate compared to those
adults; 12 mg/kg/day for children and adolescents up to receiving standard of care (intervention: 134/1001 [13%] vs.
a maximum of 800 mg daily). standard: 180/998 [18%]). While the previous Southern
5
5. We have recommended alternative induction regimens African guideline recommended CrAg screening for
for CM among patients with renal dysfunction, including patients with CD4 < 100 cells/µL, this approach will fail to
liposomal amphotericin B-based options. detect a substantial proportion of cases that occur in
6. A higher dose of fluconazole is now recommended during patients with CD4 counts between 100 cells/µL and 200
the 8-week consolidation phase for CM (800 mg daily for cells/µL. A meta-analysis estimated that the pooled global
adults; 12 mg/kg/day for children and adolescents up to prevalence of cryptococcal antigenaemia was 6.5% among
a maximum of 800 mg daily).
7. Maintenance treatment for CM is recommended to be those with CD4 count < 100 cells/µL and 2% among those
13
continued for at least 12 months and until a single CD4 with a CD4 count between 101 cells/µL and 200 cells/µL.
count is > 200 cells/µL and the HIV viral load is A post hoc analysis of REMSTART trial data revealed an
suppressed. important mortality benefit of CrAg screening and pre-
8. We have included new recommendations for the emptive treatment in subgroups of patients with a CD4
prevention, monitoring and management of flucytosine count < 100 cells/µL and with CD4 count of 101 cells/
4
toxicities. µL – 200 cells/µL. Thus, we now recommend that 200 cells/
9. Although a manometer is the most accurate way to µL should be used as the CD4 threshold below which
measure raised intracranial pressure, we have suggested patients should be screened for cryptococcal disease, where
alternative options for assessment of elevated pressure resources permit (Table 1).
when it is unavailable.
10. Patients with a positive blood CrAg test result in whom TABLE 1: Summary of recommendation 1.
CM is ruled out by LP (a negative cerebrospinal fluid Scenario Sub-recommendations
[CSF] CrAg test is the most rapid method to establish HIV-seropositive adults • Screen for cryptococcal antigenaemia on serum or
or adolescents (≥ 10 years)
plasma by reflex laboratory testing (preferred) or
clinician-initiated testing
this) should be given oral fluconazole alone as induction with a CD4 count • If clinician-initiated testing is performed, screening
< 200 cells/µL
therapy (adults: 1200 mg for 2 weeks). Antiretroviral should be restricted to adults or adolescents without
treatment may be commenced immediately. prior cryptococcal disease who are initiating or
re-initiating ART
11. We recommend immediate referral for LP in all patients • A cryptococcal antigen lateral flow assay is the
preferred method for screening (vs. a latex
with a new positive blood CrAg test who initiated ART agglutination test format)
within the 4-week period prior to the CrAg test. Among HIV-seropositive children • There are insufficient data to recommend routine
(< 10 years)
cryptococcal antigen screening in children
those with a negative CSF CrAg test (i.e. in whom CM is Patients with a new • Refer to Figure 1 and Recommendations 1, 3 and 5
excluded), ART is recommended to be continued and positive CrAg test result regarding further investigations, antifungal treatment
and timing of ART
fluconazole pre-emptive therapy should be initiated. ART was started before a • Immediately refer for LP all patients with a positive
Among those with a new diagnosis of CM during the first new CrAg-positive result blood CrAg who initiated a new ART regimen in the
previous 4 weeks
4 weeks of ART, the guideline panel thought that there was received • Evaluate for other opportunistic infections including
Patients with a negative
was clinical equipoise in terms of a decision to continue CrAg test result tuberculosis and start ART as soon as possible
or interrupt ART. ART, antiretroviral treatment; CrAg, cryptococcal antigen; LP, lumbar puncture.
http://www.sajhivmed.org.za 8 Open Access